Release of a Low Molecular Weight Fc‐Like Fragment on Reduction of Water‐Insoluble IgG Myeloma Proteins1

Abstract

Abstract. Serum from a patient with multiple myeloma exhibited an unusual concurrence of abnormalities: (1) bitypic gammopathy consisting of a whole Λ‐IgG 1 paraprotein plus a circulating Λ‐Bence Jones protein; (2) marked insolubility of the partially purified paraprotein under conditions of low ionic strength, but good solubility upon further purification; (3) release of an unusual low molecular weight fragment containing Fc antigenic determinants under standard conditions of mercaptoethanol reduction of the purified paraprotein. Evidence is presented supporting the origin of the Fc fragment from the paraprotein heavy chain and describing the requirement for 6 M urea for its dissociation from the reduced and alkylated heavy chain. The phenomenon is evidently not rare, since screening of 14 additional myeloma sera revealed one with similar euglobulin properties and an apparently similar Fc fragment abnormality. The nature and origin of the fragment in relation to previously described immunoglobulin fragments are discussed.